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Grand RoundsWeekly Evidence Brief

Hematology

Edition

30-Second Takeaway

  • Orca-T grafts markedly reduce chronic GVHD and non-relapse mortality versus tacrolimus–methotrexate prophylaxis after myeloablative allo-HSCT.
  • Anti-CD38-based quadruplets improve both progression-free and overall survival in transplant-ineligible newly diagnosed myeloma.
  • MRD-guided preemptive azacitidine can deliver durable relapse prevention in a subset of MRD-positive MDS/AML patients.

Week ending December 13, 2025

Practice-shaping updates in transplantation, myeloma therapy, and genomic risk tools

Orca-T grafts markedly improve chronic GVHD-free survival after myeloablative allo-HSCT

BLOODDec 12, 2025

In adults with acute leukemias or MDS undergoing myeloablative allo-HSCT, Orca-T significantly improved survival free from moderate-to-severe chronic GVHD versus Tac/MTX. One-year chronic GVHD-free survival was 78.0% with Orca-T versus 38.4% with Tac/MTX, with a hazard ratio of 0.26 for the primary endpoint. Moderate-to-severe chronic GVHD occurred in 12.6% of Orca-T recipients versus 44.0% with Tac/MTX, and non-relapse mortality was 3.4% versus 13.2%. GVHD- and relapse-free survival at one year favored Orca-T (63.1% vs 30.9%), while overall survival was numerically higher but not statistically different.

Anti-CD38 quadruplets improve survival in transplant-ineligible newly diagnosed myeloma

BLOOD CANCER JOURNALDec 7, 2025

In transplant-ineligible newly diagnosed myeloma, anti-CD38-based quadruplets improved progression-free and overall survival compared with triplet backbones. Across four randomized trials including 2,038 patients, pooled 60-month PFS was 64.7% with quadruplets versus 46.3% with triplets, HR 0.57. Quadruplets reduced progression risk versus both D-Rd and VRd, and improved overall survival with pooled HR 0.78 versus triplets. Network meta-analysis ranked D-VRd and I-VRd highest for complete response, progression-free survival, and overall survival among evaluated regimens.

MRD-guided azacitidine can yield durable remissions in high-risk MDS/AML

BLOODDec 8, 2025

In RELAZA2, patients with advanced MDS or AML becoming MRD-positive after chemotherapy or allo-HSCT received preemptive azacitidine for up to two years. Among 95 eligible MRD-positive patients, 63% were alive and relapse-free six months after azacitidine initiation, meeting the primary endpoint. Over half of early MRD responders maintained remission without hematologic relapse for at least two years from azacitidine start. Median treatment-free duration after stopping azacitidine was 20.8 months, with some responses ongoing beyond eight years.

Checkpoint inhibitor–associated ITP is rare but carries substantial mortality risk

BLOODDec 8, 2025

Among 86,467 adults treated with immune checkpoint inhibitors, ICI-associated immune thrombocytopenia occurred in 214 patients, an incidence of 0.25%. Lower baseline platelets, combination ICI therapy, stage 4 disease, and additional immune-related toxicities independently increased ICI-ITP risk. ICI-ITP typically developed around eight weeks after ICI initiation, with a median nadir platelet count of 41×10^9/L. Treatment included glucocorticoids, IVIG, and thrombopoietin receptor agonists, and 75.2% of patients recovered in a median 2.3 weeks.

References

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Additional Reads

Optional additional studies from this edition.

Edition context

Clinical signal

  • Engineered Treg-enriched Orca-T grafts may redefine standard GVHD prophylaxis in myeloablative matched-donor transplantation.
  • Front-line care for transplant-ineligible myeloma is shifting toward anti-CD38-containing quadruplets when feasible.
  • Prospective MRD surveillance in advanced MDS/AML identifies candidates for preemptive hypomethylating therapy with long-term benefit for some.